Objectives are characterization of molecular heterogeneity of the major classes of human plasma lipoproteins, composition and structure of the lipoprotein subspecies, and interactions among the various lipoproteins and between lipoproteins and cells. Composition of the plasma high density lipoproteins with respect to molecular subspecies, specific apolipoproteins and lipids as a function of the very low density lipoprotein composition in defined dietary, hormonal and familial hyperlipoproteinemic states is under investigation. Structure of the lipoprotein subspecies with respect to surface- exposed regions of apolipoproteins is studied by labeling the intact lipoprotein with Na I125-lactoperoxidase and subsequently isolating the apolipoprotein for localization of the label along the peptide chains. The surface-exposed regions of apolipoproteins in lipoproteins are potential receptor sites for interactions with enzymes and cell membranes. Thus, the parallel between lipoprotein substructure and the in vitro interactions of isolated plasma lipoproteins with human and sheep erythrocytes is being investigated by (1) quantitating the binding of I125-labeled lipoproteins and their partially or totally delipidated derivatives and by (2) use of the agglutinin concanavalin A and I125- concanavalin A to probe membrane properties altered by small amounts of the lipoproteins and their derivatives. Other aspects of the interaction between lipoproteins and membranes are being studied. The primary structure of the arginine-rich apolipoprotein(s) of humans and rabbits is being determined. This apolipoprotein probably plays an important role in cholesterol and/or cholesterol ester transport.